High-Load Ibrutinib Tablet Formulation With Wet Granulation

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Solution Overview

Problem

Current treatments for diseases associated with Bruton's tyrosine kinase (Btk) activity are limited in efficacy and delivery efficiency, particularly in high-load solid tablet formulations.

Innovation Solution

Development of high-load solid tablet formulations comprising ibrutinib, a Btk inhibitor, with specific excipient ratios and preparation methods like wet granulation, ensuring high ibrutinib content and optimal excipient distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional tablet formulations are used, then manufacturing is simpler, but ibrutinib delivery efficiency and therapeutic efficacy are insufficient

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs composite material formulation by combining ibrutinib with specific excipients including colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose in optimized ratios. This composite approach enhances drug delivery efficiency and therapeutic efficacy while maintaining manageable manufacturing complexity through systematic formulation design.

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If high-load ibrutinib content is achieved, then therapeutic efficacy improves, but manufacturing precision requirements increase

Engineering Contradiction:

Improveibrutinib contentVSAvoidexcipient distribution precision

Core Design Contradiction:

Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent optimizes the formulation by precisely controlling the weight percentages of each excipient component. Specifically, colloidal silicon dioxide (0.4-0.6%), croscarmellose sodium (6-8%), hydroxypropyl cellulose (1-3%), lactose monohydrate (13-15%), magnesium stearate (0.4-0.6%), and microcrystalline cellulose (8-10%) are used in defined ratios to achieve high ibrutinib content (560-840 mg per tablet) while ensuring uniform excipient distribution and meeting manufacturing precision requirements.

Inventive Principle:

Principle #35Parameter changes

3Stability of the object's composition

If wet granulation method is used, then formulation consistency improves, but manufacturing time and process complexity increase

Engineering Contradiction:

Improveformulation consistencyVSAvoidmanufacturing time

Core Design Contradiction:

Stability of the object's compositionVSLoss of time

Solution Approach 1:

The wet granulation process is implemented with preliminary preparation of granulation mixture containing ibrutinib, colloidal silicon dioxide, croscarmellose sodium, and hydroxypropyl cellulose before adding binding solution. This systematic preliminary action ensures uniform drug-excipient distribution and granulation consistency, reducing variability and rework time despite the extended processing duration of the wet granulation method itself.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS12551448B2Pharmaceutical formulations of a Bruton's tyrosine kinase inhibitor

Publication Date: 2026.02.17 PHARMACYCLICS LLC

AI summary

Described herein are pharmaceutical formulations of Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one. Also disclosed are methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.